Multi-Route Administration Delivery System Based on Tetrahedral Framework Nucleic Acids for Alleviating Type I...

Area of Science:

• Biochemistry
• Immunology
• Nanotechnology

Background:

• Type I hypersensitivity reactions are common but lack standardized treatments for diverse manifestations.
• Current therapeutic strategies do not adequately address the multi-systemic nature of these allergic responses.

Purpose of the Study:

• To develop a novel therapeutic strategy for type I hypersensitivity reactions.
• To design and evaluate a multi-route nucleic acid delivery system for allergic conditions.

Main Methods:

• A nanocomposite, tFNAs-siRNA-siRNA (TSS), was designed using tetrahedral framework nucleic acids (tFNAs) loaded with two siRNAs.
• TSS was administered via intraperitoneal injection, transdermal, and transnasal routes in allergic models.
• The effect of TSS on Gab2 and Syk gene expression, granule release, and mitochondrial Ca2+ efflux was assessed in RBL-2H3 cells.

Main Results:

• TSS successfully delivered siRNAs, downregulating Gab2 and Syk expression and inhibiting RBL-2H3 cell degranulation.
• TSS stabilized energy metabolism by hindering mitochondrial Ca2+ efflux.
• In vivo studies demonstrated TSS's potent anti-allergic effects in passive cutaneous anaphylaxis and allergic rhinitis models.

Conclusions:

• TSS presents a promising new therapeutic strategy for type I hypersensitivity reactions with multi-systemic symptoms.
• Nucleic acid-based multi-route administration delivery systems offer significant potential for treating complex allergic diseases.